Catalytic hydrogenation of imine has been known for a relatively long time. In organic synthesis, catalytic hydrogenation processes using either homogeneous catalysts or heterogeneous catalysts have played an important role. Heterogeneous catalysts are insoluble; thus they can be readily separated from the reaction mixture and generally, offer the potential for ready re-use whereas homogeneous catalysts are soluble and so difficulties can be encountered in separating the homogeneous catalyst, both the metal and the accompanying ligands, from the product. This not only presents problems with the purity of the product, but also makes the re-use of the homogeneous catalyst problematic. These catalysts are known to exhibit the advantages of catalyzing hydrogenation reactions in the synthesis routes for the preparation of various herbicides with remarkable chemical specificity under relatively mild conditions. Accordingly, there is an increased emphasis on the use of such catalysts in the preparation of herbicides on a commercial scale.
One such catalyst system which has demonstrated good industrial potential for the hydrogenation of imines is the homogeneous iridium—xyliphos catalyst system, which has found extensive applicability for the preparation of various herbicides especially in the preparation of (S)-2-chloro-N-(2-ethyl-6-methylphenyl)-N-(2-methoxy-1-methylethyl)acetamide [Hans-Ulrich Blaser, Advanced Synthesis and Catalysis, 2002, 344,17-31].
These homogeneous catalysis processes have proved valuable. It has been observed in the case of relatively large batches or on an industrial scale, that the catalysts frequently tend to become deactivated to a greater or lesser extent depending on the catalyst precursor, the substrate and the ligands that are used. In many cases, especially at elevated temperatures it is not possible to achieve complete conversion; therefore, the catalyst productivity is too low from the point of view of economic viability.
Advanced synthesis and catalysis, vol. 34, pp.17-31 (2000), discusses hydrogenation of imines using Ir-xyliphos ligand, acetic acid as a solvent and an iodide as an additive. This publication discloses that in the presence of acetic acid and iodide additive, the catalyst activity of an Iridium-xyliphos catalyst system increased by a factor of 10 and the ee increased by 5-6%. However, the simultaneous presence of acetic acid and an iodide additive is required to achieve an appreciable conversion as the catalyst system per se. In the absence of added acetic acid and iodide additive, the catalyst shows negligible turn-over-frequency and enantiomeric selectivity. The use of acetic acid requires specialized equipment constructed of a corrosion resistant material, which increases the costs. Moreover, acetic acid leads to the formation of hydrogen iodide and other metal salts, which further makes the reaction workup complicated. Thus, it is desirable to arrive at a process for asymmetric hydrogenation of an imine involving a catalyst system that avoids the presence of acetic acid and still achieve an appreciable turn-over-frequency and enantiomeric selectivity.
The chemistry of synthesis of chiral fine chemicals, pharmaceuticals and agrochemicals has become increasingly more complicated often requiring multi-step reactions involving complicated catalyst systems, such as, e.g., expensive organometallic catalyst systems. Consequently, there has been increased emphasis on the development of new catalyst systems which have high activity and selectivity and which maintain their catalytic activity for a relatively extended period of time under desired reaction conditions.
Hitherto, there have been numerous attempts in the art towards an enantiomeric selective catalyst system for effecting stoichiometric efficient asymmetric hydrogenation of imines.
U.S. Pat. No. 6,822,118 describes a process for the hydrogenation of imines with hydrogen under elevated pressure in the presence of homogeneous iridium catalysts with appropriate ligand and with or without an inert solvent, wherein the reaction mixture contains an ammonium or metal chloride, bromide or iodide and additionally an acid. The catalysts in these homogeneous processes cannot be recovered or can be recovered only with expensive separation methods, which is always associated with undesirable losses. Thus, there remains a need in the art for a process for asymmetric hydrogenation of imines involving an improved catalyst system that overcomes the disadvantages associated with these hitherto known catalysts.
Chem. Reviews, 2003, 103, 3101-3118 discloses the ferrocenyl phosphine, xyliphos and josiphos ligands for hydrogenation of imines. This literature discusses the use of iodide and acid as additives for hydrogenation of imines. The disclosed process again requires the simultaneous presence of acetic acid and an iodide additive to achieve an appreciable turn-over-frequency and enantiomeric selectivity. However, as discussed above, the simultaneous presence of acetic acid and an iodide additive is undesirable.
US 2006/089469, whose contents are incorporated herein by reference in entirety, discloses asymmetrical, chiral hydroxyl diphosphines and their use as catalysts for enantioselective synthesis. The described organophosphorus compounds are combined with metal complex precursors in order to provide a suitable catalyst system. Paragraph [0025] discloses particularly preferred catalyst systems according to the invention disclosed comprising Ru and Rh complexes containing the described ligands.
This patent teaches the preparation of a ligand [(1R, 2R, 3S)-1,2-Dimethyl-2,3-bis(diphenylphosphinomethyl)cyclopentyl] methanol, while example 6 discloses the preparation of its Rh complex. Example 7 discloses the use of the rhodium complex prepared in accordance with example 6 for various hydrogenation reactions. This exemplified catalyst system is not disclosed to have been preferred for the asymmetric hydrogenation of an imine. Moreover, all the exemplified reactions were carried out at room temperature under a hydrogen pressure of I bar, which is contrary to the finding of the present invention.
It has further been observed on an industrial scale that the catalyst systems frequently tend to become deactivated depending on the catalyst precursor, the substrate and the ligands. It has further been found that not all catalyst systems that are known in the art enable a complete conversion of the starting materials into the target product with a high enantiomeric selectivity.
S-Metolachlor is one of the most important grass herbicides for use on soyabean, maize and other various crops. The racemic form of this known herbicide contains two chiral elements, a chiral axis and a stereogenic center leading to four stereo-isomers. It later came to be known that about 95% of the herbicidal activity of metolachlor resided in the two 1-S diastereomers. This meant that the same biological effect could be produced at about 65% of the use rate of the racemic product. However, a commercially feasible process for the enantioselective manufacture of S-Metolachlor has been compared to moving in a complicated labyrinth. The search for a catalyst for the enantioselective manufacture of S-Metolachlor is likened to a walk in a labyrinth that covers the “TON-EE” space i.e. finding a catalyst with a sufficient stereospecificity (greater than 74% enantiomeric excess) as well as productivity (at least 99% conversion efficiency). Thus, finding an efficient and enantioselective catalyst for the preparation of S-Metolachlor has been a long felt and challenging need in the art of herbicide synthesis.
Thus, there is a continuous need in the art for a process that enables an enantioselective hydrogenation of imines with a high conversion as well as a high enantiomeric excess of the target product wherein the catalyst system is cost effective.